Increased production of nitric oxide in patients with hemorrhagic fever with renal syndrome--relation to arterial hypotension and tumor necrosis factor.

In 15 consecutive subjects hospitalized with nephropathia epidemica, a European form of hemorrhagic fever with renal syndrome, the plasma concentrations of nitrate plus nitrite, stable metabolites of nitric oxide, were determined. From day 3 of onset of disease the concentrations increased, peak levels being reached on days 5 to 7. Maximal plasma concentrations of nitrate plus nitrite were correlated to the degree of hypotension (r = -0.64, p = 0.02) and levels of tumor necrosis factor (TNF)-alpha (r = 0.51, p = 0.05) and soluble TNF receptors p55 and p75 (r = 0.58, p = 0.03 and r = 0.54, p = 0.04, respectively) but not to levels of interferon-gamma or interleukin-10 (p > 0.05). The results are compatible with the well-known capacity of TNF-alpha to enhance production of nitric oxide, and suggest that nitric oxide may be of physiologic importance in hemorrhagic fever with renal syndrome.